28-Day Oral Chronic Toxicity Study of Arctigenin in Rats
Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity pro...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01077/full |
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| author | Yu-jun Tan Yu-jun Tan Yu-shan Ren Yu-shan Ren Lei Gao Lei Gao Lan-fang Li Lan-fang Li Li-juan Cui Li-juan Cui Bin Li Bin Li Xin Li Xin Li Jian Yang Jian Yang Ming-zhi Wang Ming-zhi Wang Yuan-yuan Lv Yuan-yuan Lv Xiao-li Xu Xiao-li Xu Jing-chun Yao Jing-chun Yao Jing-chun Yao Zhong Liu Zhong Liu Zhong Liu Gui-min Zhang Gui-min Zhang Gui-min Zhang Jie Li Jie Li Jie Li |
| author_facet | Yu-jun Tan Yu-jun Tan Yu-shan Ren Yu-shan Ren Lei Gao Lei Gao Lan-fang Li Lan-fang Li Li-juan Cui Li-juan Cui Bin Li Bin Li Xin Li Xin Li Jian Yang Jian Yang Ming-zhi Wang Ming-zhi Wang Yuan-yuan Lv Yuan-yuan Lv Xiao-li Xu Xiao-li Xu Jing-chun Yao Jing-chun Yao Jing-chun Yao Zhong Liu Zhong Liu Zhong Liu Gui-min Zhang Gui-min Zhang Gui-min Zhang Jie Li Jie Li Jie Li |
| author_sort | Yu-jun Tan |
| collection | DOAJ |
| description | Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg. |
| first_indexed | 2024-12-21T02:50:45Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T02:50:45Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e5c9eca40ace4f54a3cad9c202c72e382022-12-21T19:18:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-09-01910.3389/fphar.2018.0107739982928-Day Oral Chronic Toxicity Study of Arctigenin in RatsYu-jun Tan0Yu-jun Tan1Yu-shan Ren2Yu-shan Ren3Lei Gao4Lei Gao5Lan-fang Li6Lan-fang Li7Li-juan Cui8Li-juan Cui9Bin Li10Bin Li11Xin Li12Xin Li13Jian Yang14Jian Yang15Ming-zhi Wang16Ming-zhi Wang17Yuan-yuan Lv18Yuan-yuan Lv19Xiao-li Xu20Xiao-li Xu21Jing-chun Yao22Jing-chun Yao23Jing-chun Yao24Zhong Liu25Zhong Liu26Zhong Liu27Gui-min Zhang28Gui-min Zhang29Gui-min Zhang30Jie Li31Jie Li32Jie Li33Shandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaShandong New Time Pharmaceutical Co., LTD., Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaNational Engineering and Technology Research Center of Chirality Pharmaceutica, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co.Ltd., Linyi, ChinaArctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.https://www.frontiersin.org/article/10.3389/fphar.2018.01077/fullArctium lappaArctigeninsub-chronic toxicitysafetydrug exposure |
| spellingShingle | Yu-jun Tan Yu-jun Tan Yu-shan Ren Yu-shan Ren Lei Gao Lei Gao Lan-fang Li Lan-fang Li Li-juan Cui Li-juan Cui Bin Li Bin Li Xin Li Xin Li Jian Yang Jian Yang Ming-zhi Wang Ming-zhi Wang Yuan-yuan Lv Yuan-yuan Lv Xiao-li Xu Xiao-li Xu Jing-chun Yao Jing-chun Yao Jing-chun Yao Zhong Liu Zhong Liu Zhong Liu Gui-min Zhang Gui-min Zhang Gui-min Zhang Jie Li Jie Li Jie Li 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats Frontiers in Pharmacology Arctium lappa Arctigenin sub-chronic toxicity safety drug exposure |
| title | 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats |
| title_full | 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats |
| title_fullStr | 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats |
| title_full_unstemmed | 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats |
| title_short | 28-Day Oral Chronic Toxicity Study of Arctigenin in Rats |
| title_sort | 28 day oral chronic toxicity study of arctigenin in rats |
| topic | Arctium lappa Arctigenin sub-chronic toxicity safety drug exposure |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01077/full |
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